Selenium is an essential nutrient and a number of biological effects have been ascribed to it. The only known selenoenzyme in animals is glutathione peroxidase. Many of the biological effects of the elements have been dissociated from glutathione peroxidase, however, so it seems certain that other active forms of selenium exist. Selenoprotein P is a rat plasma selenoprotein which has recently been purified. It can be measured by radioimmunoassay but is function is unknown. Studies supported by this grant have established that the protein is made in the liver and that plasma levels fall in selenium deficiency. Antibodies and a cDNA probe have been produced. It is proposed to characterize selenoprotein P. The stoichiometry of selenium to protein will be studied. Tissues in which it is synthesized will be determined by Northern blot analysis and its half-life will be determined in selenium-deficient and control rats. mRNA levels and production will be measured. Experiments will be done to determine the physiological function of the protein. The major hypotheses to be tested are (1) that it is a selenium transport protein and (2) that it is an oxidant defense protein. A number of experiments are planned to test its ability to protect against free-radical injury and lipid peroxidation. Its interaction with GSH will be assessed. Finally, human selenoprotein P will be purified and an assay for it will be devised. These studies will extend our understanding of the function of selenium and could lead to a better understanding of oxidant defenses.